Does clearing of axillary lymph nodes contribute to accurate staging of breast carcinoma?

The major prognostic indicator in carcinoma of the breast is the presence of metastases in axillary lymph nodes. However, 25% of patients with negative axilliary nodes by standard pathologic techniques are dead of metastatic breast carcinoma within 10 years. "Clearing" of the axillary fat has been shown to increase the yield of lymph nodes. Forty-two pathologic Stage I and II breast carcinoma specimens were cleared following routine pathologic examination to determine whether stage was changed by the clearing procedure. A total of 857 lymph nodes were recovered from 42 patients by routine techniques. Clearing increased the number of nodes found by 30%, to 1114. In the 31 node-negative patients an additional 178 nodes were identified, increasing the mean number of nodes per patient from 20 to 26. The number of additional nodes found per specimen ranged from 0 to 19. None of the additional nodes identified contained metastases. In the node-positive patients, 79 additional nodes were found by clearing, including 33 with metastases. No change in stage resulted, although the mean number of nodes per patient was increased from 22 to 30. Although an occasional positive lymph node may be overlooked by manual dissection, the rarity of this event makes routine clearing of the axillary contents impractical for carcinoma of the breast except in a research setting. Whether this conclusion applies equally to other tumors and other lymph node groups requires further study.     

Variability of the depth of supraclavicular and axillary lymph nodes in patients with breast cancer: is a posterior axillary boost field necessary?

PURPOSE: To determine the variability of the depth of supraclavicular (SC) and axillary (AX) lymph nodes in patients undergoing radiation therapy for breast cancer and to relate this variability with the patient's anterior/posterior (A/P) diameter. The dosimetric consequences of the variability in depth are explored and related to the need for a posterior axillary boost field. METHOD AND MATERIALS: In 49 patients undergoing treatment-planning computed tomography (CT) scanning in the treatment position, the maximum depth of the SC and AX lymph nodes was measured on CT images. The A/P diameter was measured at the location of the SC and AX, respectively. The relationship between the SC/AX lymph node depth and patient diameter was determined using linear regression. For an anterior SC and AX field, the relative dose to the SC and AX lymph nodes were calculated for a 6 MV photon beam. RESULTS: The maximum depth of the SC lymph nodes ranged from 2.4 to 9.5 cm (median, 4.3 cm). The depth was less than 3 cm in 4 patients, 3-6 cm in 39 (80%), and greater than 6 cm in 6 patients. There was a linear relationship between the SC lymph node depth and the A/P diameter. The depth of the SC lymph nodes in cm equals approximately one-half of the A/P diameter minus 3.5 (r(2) = 0.69). In 94% (46 of 49) of patients, the SC lymph node depth was between one-fifth and one-half of the A/P diameter.The depth of the axillary lymph nodes ranged from 1.4 to 8 cm (median, 4.3 cm). The depth was less than 3 cm in 8 patients, 3-6 cm in 32 (65%), and greater than 6 cm in 9 patients. The AX lymph node depth in cm equals approximately one-half of the A/P diameter minus 3 (r(2) = 0.81). In all patients, the AX lymph nodes were shallower than mid-depth.The depth of the SC and AX lymph nodes was within +/- 1 cm in 53% (26 of 49) of patients. The AX lymph nodes were located at >/= 1 cm shallower or greater depth than the SC in 24.5% (12 of 49) and 22.5% (11 of 49) of patients, respectively. If an anterior 6-MV beam only is used to treat the SC and AX lymph nodes in these 49 patients, the dose to the AX is within +/- 5% of the SC dose in 53% (26 of 49) patients and is 90% or more of the dose delivered in the SC in 90% (44 of 49) of patients. CONCLUSION: The maximum depth of the SC and AX lymph nodes varies widely and is related to the patient's size represented by the A/P diameter. In most patients, the AX lymph nodes lie at approximately the same depth or shallower than the SC. Therefore, the rationale for a posterior axillary boost field needs to be further assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular and axillary fields and/or the use of a higher energy beam might be reasonable.     

Assessing the status of axillary sentinel lymph nodes of breast carcinoma patients by a real-time quantitative RT-PCR assay for mammaglobin 1 mRNA

Summary The aim of the study was to assess the accuracy of a real-time quantitative RT-PCR (qRT-PCR) assay for mammaglobin 1 mRNA in the detection of metastatic breast cancer in axillary sentinel lymph nodes (SLN), comparing the results with those of qualitative RT-PCR assays and of an extensive histopathological examination. A retrospective series of 81 SLN from 72 patients and a validation series of 61 SLN from 61 patients were evaluated. In the retrospective series, the qRT-PCR assay was positive for 23 (28.4%) of the 81 SLN. The overall concordance with histopathology was 93.8%, with a sensitivity of 90.9%, a specificity of 94.9%, a positive predictive value (PPV) of 87% and a negative predictive value (NPV) of 96.6%. In the same series, qualitative RT-PCR showed an overall concordance with histopathology of 86.4%, a sensitivity of 72.7%, a specificity of 91.5%, a PPV of 76.2% and a NPV of 90%. In the validation series, including 23 patients with pure in situ carcinoma, the real-time qRT-PCR assay showed an overall concordance with the histopathologic findings of 93.4%, with a sensitivity of 75.0%, a specificity of 94.7%, a PPV of 50.0% and a NPV of 98.2%. We conclude that real-time qRT-PCR assays for mammaglobin 1 are more sensitive and specific that qualitative RT-PCR assays for the detection of metastatic breast carcinoma in axillary SLN, but it should not be regarded as a possible substitute for an extensive histopathological scrutiny of the SLN in the clinical practice.     

Does the number of lymph nodes examined in patients with lymph node-negative breast carcinoma have prognostic significance?

BACKGROUND: There are conflicting data on the prognostic significance of the number of lymph nodes examined in patients with lymph node-negative breast carcinoma. Therefore, the authors analyzed the impact of the number of tumor-free axillary lymph nodes on disease-free survival (DFS) in two distinct patient populations. METHODS: Eight hundred thirty-three consecutive patients with breast carcinoma who underwent mastectomy between 1927 and 1987 and 1094 consecutive patients with breast carcinoma who underwent with breast-conservation therapy between 1984 and 2001 were diagnosed pathologically with negative axillary lymph node status. Patients were stratified into 4 groups according to the number of lymph nodes examined: Group 1 had 1-3 lymph nodes examined, Group 2 had 4-9 lymph nodes examined, Group 3 had 10-20 lymph nodes examined, and Group 4 had >20 lymph nodes examined. RESULTS: In the mastectomy cohort, with a median follow-up of 153 months, the 10-year DFS rate was 70%, 65%, 79%, and 81% for Groups 1-4, respectively. On multivariate analysis, pathologic tumor size (P<0.001) and the number of lymph nodes examined (P=0.010) were significant predictors for long-term DFS. In the breast-conservation cohort, with a median follow-up of 53 months, the 5-year DFS rate was 90%, 91%, 92%, and 95% for Groups 1-4, respectively. On multivariate analysis, the only predictors of DFS were method of detection (clinically vs. mammographically) (P=0.003) and tumor size (P=0.035). CONCLUSIONS: The recovery of <10 lymph nodes in lymph node-negative patients who underwent mastectomy resulted in a 10-15% decreased long-term DFS rate compared with patients who had a more extensive axillary assessment. However, the number of lymph nodes examined did not have an impact on the DFS rate in a contemporary cohort of patients who underwent breast-conservation therapy, which included radiation.     

Vulvar cancer and sentinel lymph nodes: a new standard of care?

The treatment of early-stage vulvar cancer has remained surgical over time. Fortunately, less invasive surgical options have emerged, decreasing the significant morbidity associated with treatment. In the past decade, sentinel lymph node (SLN) dissection alone in select patients with vulvar cancer has been shown to be safe, feasible and has decreased surgical morbidity. In addition, multiple recent studies have reported low groin recurrence rates in women that underwent SLN dissection alone, which are similar to groin recurrence rates seen among women that underwent complete inguinal lymph node dissection. We believe SLN dissection should be the standard of care in select patients at institutions with surgeons experienced in the SLN technique. We feel caution should be used when performing SLN dissections in large vulvar lesions and in midline lesions. Further information is needed regarding the appropriate treatment of positive sentinel lymph nodes and, in particular, on the management of micrometastases.     

How many sentinel lymph nodes are enough during sentinel lymph node dissection for breast cancer?

BACKGROUND.: It remains unclear how many sentinel lymph nodes (SLNs) must be removed to accurately predict lymph node status during SLN dissection in breast cancer. The objective of this study was to determine how many SLNs need to be removed for accurate lymph node staging and which patient and tumor characteristics influence this number. METHODS.: The authors reviewed data for all patients in their prospective database with clinical tumor, lymph node, metastasis (TNM) T1 through T3, N0, M0 breast cancer who underwent lymphatic mapping at their institution during the years 1994 through 2006. There were 777 patients who had at least 1 SLN that was positive for cancer. Simple and multiple quantile regression analyses were used to determine which patient and tumor characteristics were associated with the number of positive SLNs. The baseline number of SLNs that needed to be dissected for detection of 99% of positive SLNs in the total group of patients also was determined. RESULTS.: The mean number of SLNs removed in the 777 lymph node-positive patients was 2.9 (range, 1-13 SLNs). Greater than 99% of positive SLNs were identified in the first 5 lymph nodes removed. On univariate analysis, tumor histology, patient race, tumor location, and tumor size significantly affected the number of SLNs that needed to be removed to identify 99% of all positive SLNs. On multivariate analysis, mixed ductal and lobular histology, Caucasian race, inner quadrant tumor location, and T1 tumor classification significantly increased the number of SLNs that needed to be removed to achieve 99% recovery of all positive SLNs. CONCLUSIONS.: In general, the removal of a maximum of 5 SLNs at surgery allowed for the recovery of >99% of positive SLNs in patients with breast cancer. The current findings indicated that tumor histology, patient race, and tumor size and location may influence this number.     

Is axillary clearance the standard of care for breast cancer patients with sentinel node involvement?

Sentinel node biopsy (SNB) has become accepted for staging the axilla in early breast cancer with avoidance of axillary lymph node dissection (ALND) in patients with negative SNB. For those with positive SNB, the standard surgical management is ALND; however, this approach is increasingly being challenged. The central problem is that it is not possible to preoperatively predict whether the SNB will be positive, and it is even more difficult to determine the likelihood of nonsentinel node positivity. Various histopathological features indicate increased risk of nonsentinel node metastasis, including size of SNB metastasis, presence of lymphovascular invasion, multifocality, number of involved sentinel nodes and, conversely, the number of negative sentinel nodes. These features have been combined to produce predictive nomograms but, understandably, these still lack precision. Presently, the decision to avoid ALND will depend upon both the clinician and the patient's impression of risk, but if either requires assurance that no residual axillary disease remains, a completion clearance will be required.     

Should internal mammary lymph nodes in breast cancer be a target for the radiation oncologist?

PURPOSE: The elective treatment of internal mammary lymph nodes (++IMNs) in breast cancer is controversial. Previous randomized trials have not shown a benefit to the extended radical mastectomy or elective IMN irradiation overall, but a survival benefit has been suggested by some for subgroups of patients with medial tumors and positive axillary lymph nodes. The advent of effective systemic chemotherapy and potential for serious cardiac morbidity have also been factors leading to the decreased use of IMN irradiation during the past decade. The recent publishing of positive trials testing postmastectomy radiation that had included regional IMN irradiation has renewed interest in their elective treatment. The purpose of this study is to critically review historical and new data regarding IMNs in breast cancer. METHODS AND MATERIALS: The historical incidence of occult IMN positivity in operable breast cancer is reviewed, and the new information provided by sentinel lymph node studies also discussed. The results of published randomized prospective trials testing the value of elective IMN dissection and/or radiation are analyzed. The data regarding patterns of failure following elective IMN treatment is studied to determine its impact on local-regional control, distant metastases, and survival. A conclusion is drawn regarding the merits of elective IMN treatment based on this review of the literature. RESULTS: Although controversial, the existing data from prospective, randomized trials of IMN treatment do not seem to support their elective dissection or irradiation. While it has not been shown to contribute to a survival benefit, the IMN irradiation increases the risk of cardiac toxicity that has effaced the value of radiation of the chest wall in reducing breast cancer deaths in previous randomized studies and meta-analyses. Sentinel lymph node mapping provides an opportunity to further evaluate the IMN chain in early stage breast cancer. Biopsy of "hot" nodes may be considered in the future to select patients who are most likely to benefit from additional regional therapy to these nodes. CONCLUSIONS: Irradiation of the IMN chain in conjunction with the chest wall and supraclavicular region should be considered only for those with pathologically proven IMNs with the goal of improving tumor regional control.     

Is risk of axillary lymph node metastasis associated with proximity of breast cancer to the skin?

Introduction Risk of axillary lymph node metastasis, the most important predictor of disease-free and overall survival in breast cancer patients, is estimated primarily from histologic features of the primary cancer including tumor size, histologic type and grade, and hormone receptor expression. Based upon a clinical impression, and research showing that palpable cancers are more likely to be node positive, we hypothesized that primary breast cancers more proximal to the skin of the breast are more likely to be positive for axillary lymph node metastasis.Methods This is a retrospective medical record review of 209 women with stage T1 or T2 (≤5.0 cm) invasive breast cancer who received dedicated breast ultrasound at a single mammography clinic in Columbia, South Carolina, between 1997 and 2002.Results None of the 26 cancers more than 14 mm from the skin had metastasized to axillary lymph nodes. In logistic regression modeling only tumor size, histologic grade and tumor proximity to the skin (as a categorical variable) were significantly associated with odds of axillary metastasis. Among cancers within 14 mm of the skin, proximity was not an independent predictor.Conclusions Stage T1 and T2 breast cancers located less proximally to the skin may be less likely to spread to the axillary lymph nodes. We observed what appears to be a threshold at approximately 14 mm from the skin (based upon this group of patients): none of 26 cancers below this level had spread to axillary nodes. Further research is needed to confirm these provocative findings.     

Irradiation after surgery for breast cancer patients with primary tumours and one to three positive axillary lymph nodes: yes or no?

Objective and Methods

We retrospectively analyzed clinicopathologic features and survival in breast cancer patients who had T1 or T2 primary tumours and 1–3 histologically involved axillary lymph nodes and who were treated with modified radical mastectomy without adjuvant radiotherapy (rt). We also explored prognosis to find the high- and low-risk groups.

Results

From May 2001 to April 2005, 368 patients treated at Tianjin Tumor Hospital met the study criteria. The 5- and 8-year rates were 7.2% and 10.7% for locoregional recurrence (lrr), 85.1% and 77.7% for disease-free survival (dfs), and 92.8% and 89.3% for overall survival (os). Multivariate Cox regression analysis showed that age, tumour size, estrogen receptor (er) status, and lymphovascular invasion (lvi) were independent prognostic factors for lrr and dfs. Based on 4 patient-related factors that indicate poor prognosis (age < 40 years, tumour > 3 cm, er negativity, and lvi), the high-risk group (patients with 3 or 4 factors, accounting for 12.5% of the cohort) had 5- and 8-year rates of 24.3% and 36.9% for lrr, 57.2% and 39.2% for dfs, and 74.8% and 43.8% for os compared with 5.0% and 7.1% for lrr, 88.9% and 83.1% for dfs, 91.6% and 83.4% for os in the low-risk group (patients with 0–2 factors, accounting for 87.5% of the cohort; p < 0.001).

Conclusions

Our study identified several risk factors that correlated independently with a greater incidence of lrr and distant metastasis in patients with T1 and T2 breast cancer and 1–3 positive nodes. Patients with 0–2 risk factors may not be likely to benefit from post-mastectomy rt, but patients with 3–4 risk factors may need rt to optimize locoregional control and improve survival.     

Sentinel lymph node biopsy for breast cancer: How many nodes are enough?

INTRODUCTION: Sentinel lymph node (SLN) biopsy using blue dye and radioisotope often results in the removal of multiple SLNs. We sought to determine whether there is a point where the surgeon can terminate the procedure without sacrificing accuracy. METHODS: One thousand one hundred ninety-seven patients from University of Michigan and the Mayo Clinic undergoing SLN biopsy formed the study population. Surgeons removed all SLNs until counts within the axilla were less than 10% of the highest node ex vivo and recorded the order in which they were removed. RESULTS: The mean number of SLNs removed per patient was 2.5 (range 1-9). Approximately 42% of patients had three or more lymph nodes removed, while 19% had four or more lymph nodes removed. Eighteen percent of patients (132/725) at University of Michigan and 22% (103/472) at Mayo Clinic had a positive SLN. Ninety-eight percent (231/235) of patients with lymph node metastases were identified by the 3rd SLN while 100% were identified by the 4th SLN. CONCLUSION: Among patients undergoing SLN biopsy for breast cancer, the only positive SLN is rarely identified in the 4th or higher node. Terminating the procedure at the 4th node may lower the cost of the procedure and reduce morbidity.